Induction Strategies (induction + strategy)

Distribution by Scientific Domains


Selected Abstracts


Preclinical evaluation of tolerance induction protocols and islet transplantation in non-human primates

IMMUNOLOGICAL REVIEWS, Issue 1 2001
Sean P. Montgomery
Summary: Non-human primate studies of tolerance induction strategies in solid organ transplantation represent a critical bridge between studies in rodents and humans. Our work demonstrates that strategies involving the blockade of co-stimulatory molecules, especially the CD40,CD154 pathway, have great potential for clinical adaptation. While the combination of anti-CD154 antibody with blockade of the CD28 pathway reduced donor antibody production, graft survival was not significantly improved over that achieved with anti-CD154 antibody alone. Moreover, although long courses of steroids seem to interfere with this approach, it may be possible to combine blockade of the CD40,CD154 pathway with other conventional immunosuppressants without sacrificing efficacy. This is a key issue for reducing the risk associated with eventual clinical trials. Work in the non-human primate islet transplant model demonstrates that viable islets can be recovered, isolated and infused in a reliable fashion. It also confirms the efficacy of a steroid sparing approach to immunosuppression for islet transplantation. These data have been expanded to the kidney allograft model, setting the stage for kidney islet transplantation studies. Overall, tolerance induction and islet transplant studies in non-human primates permit the preclinical screening of promising immunomodulatory approaches developed in rodents and reduce the inherent uncertainties associated with adapting new regimens to the clinic. [source]


Effects of feeding and induction strategy on the production of BmR1 antigen in recombinant E. coli

LETTERS IN APPLIED MICROBIOLOGY, Issue 5 2009
A. Norsyahida
Abstract Aim:, To investigate the effects of feeding and induction strategies on the production of BmR1 recombinant antigen. Methods and Results:, Fed-batch fermentation was studied with respect to the specific growth rate and mode of induction to assess the growth potential of the bacteria in a bioreactor and to produce high yield of BmR1 recombinant antigen. Cells were grown at a controlled specific growth rate (,set) during pre-induction, followed by constant feeding postinduction. The highest biomass (24·3 g l,1) was obtained during fed-batch process operated at ,set of 0·15 h,1, whereby lower ,set (0·075 h,1) gave the highest protein production (9·82 mg l,1). The yield of BmR1 was increased by 1·2-fold upon induction with 1 mmol l,1 IPTG (isopropyl-,- d -thiogalactoside) compared to using 5 mmol l,1 and showed a further 3·5-fold increase when the culture was induced twice at the late log phase. Conclusions:, Combination of feeding at a lower ,set and twice induction with 1 mmol l,1 IPTG yielded the best result of all variables tested, promising an improved method for BmR1 production. Significance and Impact of the Study:, This method can be used to increase the production scale of the BmR1 recombinant antigen to meet the increasing demand for Brugia RapidÔ, a commercial diagnostic test for detection of brugian filariasis. [source]


Designing an Inducer-Feeding Schedule To Enhance Production of Recombinant Protein in Escherichia coli by Microbial Reaction Engineering

BIOTECHNOLOGY PROGRESS, Issue 3 2008
Jesus M. Gonzalez
Metabolic constraints during the production of recombinant protein in Escherichia coli impede the efficient utilization of resources by the cells, thus reducing their production potential. In order to minimize these adverse effects, we have proposed to segregate the cell population into two groups: the first one formed by non-induced cells, growing at a high specific growth rate and rapidly contributing cells to the system, and the second one formed by fully induced cells, growing slowly but using the cell machinery to express the target protein. An adequate balance between these two populations should maximize the protein expression in a given system. This segregation is accomplished experimentally by taking advantage of the "all or none" phenomenon, in which at subsaturated inducer conditions the cells are either fully induced or fully uninduced. Based on this two-population theory, a mathematical model was developed in which a parameter , was defined as the fraction of the fully induced cells in the total population. In this study three different induction strategies were investigated and their effect on the protein production was established. It was found that the linear increase of this fraction, achieving maximum induction (, = 1) only at the end of the fermentation and with a slope m = 0.15 gave the best results. Finally these results were validated experimentally with the finding that they closely match the mathematical simulation with a 26% increase in protein production with respect to the conventional induction approach described. [source]


Effects of feeding and induction strategy on the production of BmR1 antigen in recombinant E. coli

LETTERS IN APPLIED MICROBIOLOGY, Issue 5 2009
A. Norsyahida
Abstract Aim:, To investigate the effects of feeding and induction strategies on the production of BmR1 recombinant antigen. Methods and Results:, Fed-batch fermentation was studied with respect to the specific growth rate and mode of induction to assess the growth potential of the bacteria in a bioreactor and to produce high yield of BmR1 recombinant antigen. Cells were grown at a controlled specific growth rate (,set) during pre-induction, followed by constant feeding postinduction. The highest biomass (24·3 g l,1) was obtained during fed-batch process operated at ,set of 0·15 h,1, whereby lower ,set (0·075 h,1) gave the highest protein production (9·82 mg l,1). The yield of BmR1 was increased by 1·2-fold upon induction with 1 mmol l,1 IPTG (isopropyl-,- d -thiogalactoside) compared to using 5 mmol l,1 and showed a further 3·5-fold increase when the culture was induced twice at the late log phase. Conclusions:, Combination of feeding at a lower ,set and twice induction with 1 mmol l,1 IPTG yielded the best result of all variables tested, promising an improved method for BmR1 production. Significance and Impact of the Study:, This method can be used to increase the production scale of the BmR1 recombinant antigen to meet the increasing demand for Brugia RapidÔ, a commercial diagnostic test for detection of brugian filariasis. [source]